Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/104296
Title: Mericitabine and Either Boceprevir or Telaprevir in Combination with Peginterferon Alfa-2a plus Ribavirin for Patients with chronic Hepatitis C Genotype 1 Infection and Prior Null Response: The Randomized DYNAMO 1 and DYNAMO 2 Studies.
Author: Wedemeyer, Heiner
Forns, Xavier
Hézode, Christophe
Lee, Samuel S
Scalori, Astrid
Voulgari, Athina
Le Pogam, Sophie
Nájera, Isabel
Thommes, James A
Keywords: Hepatitis C
Virus de l'hepatitis C
Antiretrovirals
Anèmia
Cirrosi hepàtica
Assaigs clínics
Hepatitis C
Hepatitis C virus
Antiretroviral agents
Anemia
Hepatic cirrhosis
Clinical trials
Issue Date: 11-Jan-2016
Publisher: Public Library of Science (PLoS)
Abstract: Most patients with chronic hepatitis C virus (HCV) genotype 1 infection who have had a pre- vious null response ( < 2-log 10 reduction in HCV RNA by treatment week 12) to peginter- feron/ribavirin (PegIFN/RBV) do not achieve a sustained virological response (SVR) when re-treated with a first-generation HCV protease inhibitor (PI) administered in combination with PegIFN/RBV. We studied the incremental benefits associated with adding mericitabine (nucleoside analog inhibitor of HCV polymerase) to PI plus PegIFN alfa-2a/RBV-based therapy in two double-blind randomized multicenter phase 2 trials (with boceprevir in DYNAMO 1, and with telaprevir in DYNAMO 2). The primary endpoint in both trials was SVR, defined as HCV RNA < 25 IU/mL 12 weeks after the end of treatment (SVR12). Over- all, the addition of mericitabine to PI plus PegIFN alfa-2a/RBV therapy resulted in SVR12 rates of 60 - 70% in DYNAMO 1 and of 71 - 96% in DYNAMO 2. SVR12 rates were similar in patients infected with HCV genotype 1a and 1b in both trials. The placebo control arms in both studies were stopped because of high rates of virological failure. Numerically lower relapse rates were associated with longer treatment with mericitabine (24 versus 12 weeks), telaprevir-containing regimens, and regimens that included 48 weeks of PegIFN alfa-2a/RBV therapy. No mericitabine resistance mutations were identified in any patient in either trial. The addition of mericitabine did not add to the safety burden associated with either telaprevir or boceprevir-based regimens. These studies demonstrate increased SVR rates and reduced relapse rates in difficult-to-treat patients when a nucleoside polymerase inhibitor with intermediate antiviral potency is added to regimens containing a first-genera- tion PI.
Note: Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0145409
It is part of: PLoS One, 2016, vol. 11, num. 1, p. e0145409
Related resource: https://doi.org/10.1371/journal.pone.0145409
URI: http://hdl.handle.net/2445/104296
ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Medicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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